The overall objective of this research program is to further our understanding of regulatory mechanisms controlling the immune system. This objective will be approached by delineating the various mechanisms by which regulatory cell interactions, and the molecules involved in such interactions, are ultimately translated into immune responses. Since there is good reason to believe that the IgE antibody system provides a particularly sensitive and illuminating window through which to view mechanisms of regulatory control of the immune system, we are focusing our attention on the regulatory processes governing the IgE system. Recently, we have discovered a family of regulatory molecules that interact with one another, and with certain definable lymphoid cells that appear to be selectively concerned with the IgE system--namely, those that express IgE-specific Fc receptors (FcRepsilon). The cascade of cellular and molecular events in which these constituents play definable roles could reflect processes that are inherent in the control mechanisms concerned with other aspects of the immune system. Therefore, this research program is oriented toward extrapolating information derived from studies defining the cellular and molecular interactions that control expression of IgE in such a way as to guide the development of new experimental approaches for delineating control mechanisms participating in expression of other immunoglobulin isotypes, and certain types of cell mediate immune responses, in experimental animals. Collectively, these studies should considerably widen our understanding of how immune regulation evolves and, under normal circumstances, maintains a steady state of maximal protection of the host.